Genomics – A programmer’s guide

https://github.com/quinlan-lab/applied-computational-genomic...

Both Gil and Peter have done some incredible things in this space, but the language of scientists can be difficult to understand by a lay audience.

My experience has been translating domain data into spark has a 100X improvement in data analysis.

Reference for "famously"?

[0] https://truwl.com/

I was taught a decade ago that rolling your own in genomics isn't as bad of a decision as it seems.

You may (at your own risk) take a look at

https://opensnp.org/

Those mutation descriptions are called HGVS (Human Genome Variation Society) nomenclature. In the example you give, "c." means that it's in a (protein) coding region, 345 is the position within the region, and G>E would be the change (although E isn't a valid "letter" in DNA sequence, even if you allow ambiguity codes -- you'd normally see something like G>T there instead).

Complications include:

1) You need to know which gene this is relative to.

2) The "coding sequence" for the gene isn't always perfectly defined, due to splice variation and different versions of the annotation. Ideally, you'd see this code relative to a specific splice variant (which might have an ENST identifier, from http://www.ensembl.org/). But it depends...

More at http://varnomen.hgvs.org/ if you're curious.

On the other hand, as a person who’s worked on sequencing software I’ve found the biochemistry knowledge to only be incidentally useful - though I may be underestimating some of the “basic” assumptions that were used day to day.

The reason I'm recommending it is the quality of its interfaces. It can seamlessly handle (input or output) virtually any kind of file you throw at it (SAM, BAM, CRAM). I can't say the same for a lot of other software I have run into in this space.

[1]: https://github.com/samtools/htslib

[2]: https://gist.github.com/PoisonAlien/350677acc03b2fbf98aa

There are several next generation sequencing technologies:

1) short read - Illumina - dominates most next-generation sequencing 2) long read - nanopore or pacbio.

These have very different analysis methods, have measurement errors that are very different, and even have different file formats, etc.

Short read is far more common, so you're probably in the "Data Analysis" of this:

https://www.youtube.com/watch?v=fCd6B5HRaZ8

But you need to know about the adapters and indices (how multiple samples can be sequenced at the same time).

But as another commenter mentions, knowing some particulars about the project would really help know what sort of tutorial would be appropriate. You'll need to also know about the biology of the application, in addition to understanding the sequencing technology.

Animals tend to have the same number of chromosomes at all times, and they tend to come in pairs that are nearly identical. There are various ways of mapping chromosomes that yield unique fingerprints that are stable under the level of variation we typically see in a species (see restriction mapping for example), so we can take a particular fingerprint and call it chromosome 1 or 2 or whatever. Animals have two copies of chromosome 1 and two copies of chromosome 2, etc. There are individuals who don't, who have a single copy of one or extra copies, and this causes problems, such as Turner syndrome. Similarly, when animals reproduce, each parent produces a germ cell (sperm or egg) that has one of each of the chromosome pairs. One of the reasons that many hybrids like mules are sterile or nearly infertile is that their chromosomes, coming from different species, aren't in pairs, so when they pass on half of them, there may be necessary hunks of DNA that just aren't passed on.

Other species have different numbers of copies of chromosomes, and may vary. Depending on point in lifecycle and conditions, some plants range from two copies to hundreds. Dinoflagellates tend to have four for interesting reasons that I believe are related to the Byzantine generals problem.

There is no XY chromosome. Females in mammals follow the normal pattern with the X chromosome: they have two of them and they are passed on like any other chromosome. Males are weird. They have one copy of X and a copy of a shrunken chromosome called Y. Note that this is only mammals. Birds and reptiles have a totally different set of chromosomes for sex determination, and in some vertebrate orders the chromosomes don't fully determine sex. Incubation temperature often changes it.

The red chunks are its DNA. But they're 'chunky' because the 'whole genome' is partitioned into 23 chunk - each chunk is a 'chromosome'. And each chromosome comes as a pair. And in the movie you can see the cell split the pairs, where one set goes to one cell, and the other set goes to the other.

If you notice, in the cells just prior to 'condensing', the nuclei (red stuff) looks kind of brain-like in its topology. Those are the chromosomes as well, just relaxed and spread out.

[1] https://www.youtube.com/watch?v=N97cgUqV0Cg

Each chromosome is either an autosome or sex chromosome. The autosomes are chr1 to chr22. All people (excepting those with chromosomal disorders, like trisomy 21) have two copies of each autosome, with one copy coming from each parent. Then, for the sex chromosomes:

* If you're male, you get an X chromosome from your mom and a Y chromosome from your dad.

* If you're female, you get an X chromosome from your mom and another X chromosome from your dad.

So, yes, "two copies of each chromosome" and "two copies of the genome" are the same concept, since the genome consists of chromosomes.

Which phenomena are you referring to exactly? That we have two copies of each chromosome and if they mean we have two copies of the human genome?

> Are there two copies of the XY chromosome, too?

Each of our non-sex cells[1] contain two sex chromosomes: one from our father and one from our mother. Since your mother always inherits her X chromosome, your sex is determined by which sex chromosome you got from your father. If you are a female (XX), your father passed on his X chromosome. If you are a male (XY), your father passed on his Y chromosome.

This rule makes for some interesting inferences. For example, your father in turn got his X chromosome from your grandmother and his Y chromosome from your grandfather (both on your father side, of course). Your mother, on the other hand, got his X chromsome from both your grandparents on her side.

So if you're a male, your Y chromosome was passed on from your grandfather on your father's side. If you're a female, one of your X chromosome comes from your grandmother on father's side, but your other X chromosome may come from either of your grandparents on your mother's side.

You can trace this Y-chromosome lineage back to what's called the Y-Chromosomal Adam, which is the last universal common ancestor of all currently living human males[2]. You can make a similar inference using your mitochondrial genome[3] and arrive at what we call the Mitochondrial Eve[4].

Our sex cells[5] are different, since they only have one copy of our chromosome set. The number of the chromosome set we have is called ploidy[6] and so our sex cells are haploid cells, as opposed to our non-sex cells, which are called diploid.

If you're a male, a single mature sperm cell in your body contains either the X or Y chromosome. For females it's different, since they only have the X chromosome, all their mature cells contain only one copy of the X chromosome.

[1] https://en.wikipedia.org/wiki/Somatic_cell

[2] https://en.wikipedia.org/wiki/Y-chromosomal_Adam

[3] https://en.wikipedia.org/wiki/Mitochondrial_DNA

[4] https://en.wikipedia.org/wiki/Mitochondrial_Eve

[5] https://en.wikipedia.org/wiki/Gamete

[6] https://en.wikipedia.org/wiki/Ploidy

I hope it was useful. It is just an introductory jargon-free guide. You can find more on Ensembl and Wikipedia.